The m6A methyltransferase METTL3 contributes to Transforming Growth Factor-beta-induced epithelial-mesenchymal transition of lung cancer cells through the regulation of JUNB

N6-Methyladenosine (m6A) is the most common internal chemical modification of mRNAs involved in many pathological processes including various cancers. In this study, we investigated the role of m6A methyltransferase METTL3 in TGF-β-induced epithelial-mesenchymal transition (EMT) of lung cancer cell lines. The expression of METTL3 and m6A RNA modification were increased during TGF-β-induced EMT of A549 and LC2/ad lung cancer cells. Knockdown of METTL3 inhibited TGF-β-induced morphological conversion of the cells, enhanced cell migration potential and the expression changes of EMT-related marker genes such as CDH1/E-cadherin, FN1/Fibronectin and VIM/Vimentin. Mechanistic investigations revealed that METTL3 knockdown decreased the m6A modification, total mRNA level and mRNA stability of JUNB, one of the important transcriptional regulators of EMT. Over-expression of JUNB partially rescued the inhibitory effects of METTL3 knockdown in the EMT phenotypes. This study demonstrates that m6A methyltransferase METTL3 is indispensable for TGF-β-induced EMT of lung cancer cells through the regulation of JUNB. •METTL3 expression is increased in TGF-β-induced EMT of lung cancer cells.•Knockdown of METTL3 antagonizes TGF-β-induced EMT and cell migration.•METTL3 regulates the m6A modification, total level and stability of JUNB mRNA.•JUNB partially recovers TGF-β-induced EMT phenotypes inhibited by METTL3 knockdown.